Research Topics
Genomes and Genes
| severe combined immunodeficiencySummarySummary: Group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. It is inherited as an X-linked or autosomal recessive defect. Mutations occurring in many different genes cause human SCID. Top Publications
Research Grants
| Scientific Experts
|
Detail Information
Publications
LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1S Hacein-Bey-Abina
INSERM Unit 429, Cedex 15, France
Science 302:415-9. 2003We have previously shown correction of X-linked severe combined immunodeficiency [SCID-X1, also known as gamma chain (gamma(c)) deficiency] in 9 out of 10 patients by retrovirus-mediated gamma(c) gene transfer into autologous CD34 bone ..
Gene therapy for immunodeficiency due to adenosine deaminase deficiencyAlessandro Aiuti
San Raffaele Telethon Institute for Gene Therapy, Milan, Italy
N Engl J Med 360:447-58. 2009We investigated the long-term outcome of gene therapy for severe combined immunodeficiency (SCID) due to the lack of adenosine deaminase (ADA), a fatal disorder of purine metabolism and immunodeficiency.
Generation of knockout rats with X-linked severe combined immunodeficiency (X-SCID) using zinc-finger nucleasesTomoji Mashimo
Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto, Japan
PLoS ONE 5:e8870. 2010..Recently, zinc-finger nucleases (ZFNs) were successfully used to create genome-specific double-stranded breaks and thereby induce targeted gene mutations in a wide variety of organisms including plants, drosophila, zebrafish, etc...- Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiencyA Puel
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892 1674, USA
Nat Genet 20:394-7. 1998b>Severe combined immunodeficiency (SCID) is caused by multiple genetic defects. The most common form of SCID, X-linked SCID (XSCID), results from mutations in IL2RG (ref... - Severe combined immunodeficiency. A model disease for molecular immunology and therapyAlain Fischer
INSERM U429, Hopital Necker Enfants Malades, Paris, France
Immunol Rev 203:98-109. 2005..SCID is thus a disease model for experimental therapy in the hematopoietic system... - Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapySalima Hacein-Bey-Abina
Laboratoire INSERM, , Paris, France
N Engl J Med 346:1185-93. 2002BACKGROUND: X-linked severe combined immunodeficiency due to a mutation in the gene encoding the common gamma (gamma(c)) chain is a lethal condition that can be cured by allogeneic stem-cell transplantation... - Highly efficient endogenous human gene correction using designed zinc-finger nucleasesFyodor D Urnov
Sangamo BioSciences, Inc, Pt. Richmond Tech Center 501, Canal Blvd, Suite A100 Richmond, California 94804, USA
Nature 435:646-51. 2005..We observe comparably high frequencies in human T cells, raising the possibility of strategies based on zinc-finger nucleases for the treatment of disease... - Integration of retroviral vectors induces minor changes in the transcriptional activity of T cells from ADA-SCID patients treated with gene therapyBarbara Cassani
San Raffaele Telethon Institute for Gene Therapy HSR TIGET, Milan, Italy
Blood 114:3546-56. 2009..We evaluated the genomic impact of RV integration in T lymphocytes from adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) patients 10 to 30 months after infusion of autologous, genetically corrected CD34(+) cells... - Efficacy of gene therapy for X-linked severe combined immunodeficiencySalima Hacein-Bey-Abina
Department of Biotherapy, Necker Enfants Malades Hospital, Paris, France
N Engl J Med 363:355-64. 2010..We reviewed long-term outcomes after gene therapy in nine patients with X-linked severe combined immunodeficiency (SCID-X1), which is characterized by the absence of the cytokine receptor common gamma chain. - Development of a routine newborn screening protocol for severe combined immunodeficiencyMei W Baker
Wisconsin State Laboratory of Hygiene, University of Wisconsin School of Medicine and Public Health, Madison, Wis 53706, USA
J Allergy Clin Immunol 124:522-7. 2009b>Severe combined immunodeficiency (SCID) is characterized by the absence of functional T cells and B cells. Without early diagnosis and treatment, infants with SCID die from severe infections within the first year of life. - Reticular dysgenesis (aleukocytosis) is caused by mutations in the gene encoding mitochondrial adenylate kinase 2Ulrich Pannicke
Institute for Transfusion Medicine, University of Ulm, Ulm, Germany
Nat Genet 41:101-5. 2009..These observations suggest that reticular dysgenesis is the first example of a human immunodeficiency syndrome that is causally linked to energy metabolism and that can therefore be classified as a mitochondriopathy... - Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patientsSteven J Howe
Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, University College London, London, United Kingdom
J Clin Invest 118:3143-50. 2008.... - A critical role for IL-21 in regulating immunoglobulin productionKatsutoshi Ozaki
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1674, USA
Science 298:1630-4. 2002..all share the common cytokine receptor gamma chain, gammac, which is mutated in humans with X-linked severe combined immunodeficiency disease (XSCID)... - Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1Salima Hacein-Bey-Abina
Department of Biotherapy, Hopital Necker Enfants Malades, Assistance Publique Hopitaux de Paris AP HP, Universite Rene Descartes, Paris, France
J Clin Invest 118:3132-42. 2008..Successful chemotherapy was associated with restoration of polyclonal transduced T cell populations. As a result, the treated patients continued to benefit from therapeutic gene transfer... - Unrelated cord blood transplantation for severe combined immunodeficiency and other primary immunodeficienciesC Diaz de Heredia
Department of Paediatric Haematology and Oncology, Hospital Vall d Hebron, Barcelona, Spain
Bone Marrow Transplant 41:627-33. 2008..No patient is intravenous immunoglobulin (IVIg) replacement therapy-dependent. UCB transplantation is a valid option for children with PID who lack an HLA-identical sibling donor... - Identification of severe combined immunodeficiency by T-cell receptor excision circles quantification using neonatal guthrie cardsYoichi Morinishi
Department of Pediatrics, National Defense Medical College, Saitama, Japan
J Pediatr 155:829-33. 2009To assess the feasibility of T-cell receptor excision circles (TRECs) quantification for neonatal mass screening of severe combined immunodeficiency (SCID). - B-cell recovery after stem cell transplantation of Artemis-deficient SCID requires elimination of autologous bone marrow precursor-B-cellsMirjam van der Burg
Department of Immunology, Erasmus MC, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands
Haematologica 91:1705-9. 2006..Apparently, occupation of the precursor-B-cell niches is a potential dominant factor influencing repopulation of a functional B-cell compartment in B-negative SCID... - Modulation of hematopoiesis in mice with a truncated mutant of the interleukin-2 receptor gamma chainK Ohbo
Department of Microbiology, Tohoku University School of Medicine, Sendai, Japan
Blood 87:956-67. 1996..Mutations of the human gamma chain cause the X-linked severe combined immunodeficiency (XSCID), showing that T and natural killer cells absolutely require the gamma chain for their .. - Neonatal diagnosis of severe combined immunodeficiency leads to significantly improved survival outcome: the case for newborn screeningLucinda Brown
Department of Clinical Immunology, Great Ormond Street Hospital National Health Service Trust, London, UK
Blood 117:3243-6. 2011b>Severe combined immunodeficiency (SCID) carries a poor prognosis without definitive treatment by hematopoietic stem cell transplantation... - Simultaneous quantification of recent thymic T-cell and bone marrow B-cell emigrants in patients with primary immunodeficiency undergone to stem cell transplantationAlessandra Sottini
Diagnostics Department, Spedali Civili di Brescia, Brescia, Italy
Clin Immunol 136:217-27. 2010..In other patients, TRECs and KRECs number remained very low for the entire period of study... - A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiencySalima Hacein-Bey-Abina
N Engl J Med 348:255-6. 2003 - Reduced central tolerance in Omenn syndrome leads to immature self-reactive oligoclonal T cellsRaz Somech
Cancer Research Center, Safra Children s Hospital, Sheba Medical Center, Tel Hashomer and Sackler School of Medicine, Tel Aviv, Israel
J Allergy Clin Immunol 124:793-800. 2009..Dysregulations of the central and peripheral immune tolerance, mediated by the protein autoimmune regulator (AIRE) and regulatory T cells, respectively, were proposed as possible mechanisms of this aberrant inflammatory process... - High-throughput multiplexed T-cell-receptor excision circle quantitative PCR assay with internal controls for detection of severe combined immunodeficiency in population-based newborn screeningJacalyn L Gerstel-Thompson
New England Newborn Screening Program, University of Massachusetts Medical School, Jamaica Plain, MA 02130, USA
Clin Chem 56:1466-74. 2010..detects the absence of functional T cells and has a demonstrated clinical validity for detecting severe combined immunodeficiency (SCID) in infants... - Update on gene therapy for adenosine deaminase-deficient severe combined immunodeficiencyFrancesca Ferrua
San Raffaele Telethon Institute for Gene Therapy, Milan, Italy
Curr Opin Allergy Clin Immunol 10:551-6. 2010The present review describes the recent progress in the treatment of adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) using autologous gene-modified hematopoietic stem cells, comparing immune reconstitution with .. - Immune reconstitution in ADA-SCID after PBL gene therapy and discontinuation of enzyme replacementAlessandro Aiuti
Nat Med 8:423-5. 2002 - Severe cutaneous papillomavirus disease after haemopoietic stem-cell transplantation in patients with severe combined immune deficiency caused by common gammac cytokine receptor subunit or JAK-3 deficiencyCaroline Laffort
, , , Paris, France
Lancet 363:2051-4. 2004..That genetic causes are the only predisposing factor to be identified for severe combined immune deficiency, suggests that natural-killer cells or gammac/JAK-3-dependent signalling in keratinocytes could have a role in anti-HPV immunity... - Early determinants of long-term T-cell reconstitution after hematopoietic stem cell transplantation for severe combined immunodeficiencyJose A Borghans
Department of Immunology, University Medical Center Utrecht, The Netherlands
Blood 108:763-9. 2006The immune system of patients with severe combined immunodeficiency (SCID) reconstitutes to a large extent during the first years after hematopoietic stem cell transplantation (HSCT)... - Increased hydrophobicity at the N terminus/membrane interface impairs gating of the severe combined immunodeficiency-related ORAI1 mutantIsabella Derler
Institute for Biophysics, University of Linz, Altenbergerstrasse 69, 4040 Linz, Austria
J Biol Chem 284:15903-15. 2009..In conclusion, the increase in hydrophobicity at the N terminus/membrane interface represents the major cause for yielding non-functional ORAI1 channels... - Systematic evidence review of newborn screening and treatment of severe combined immunodeficiencyEllen A Lipstein
Center for Child and Adolescent Health Policy, Mass General Hospital for Children, Boston, Massachusetts, USA
Pediatrics 125:e1226-35. 2010b>Severe combined immunodeficiency (SCID) is a group of disorders that leads to early childhood death as a result of severe infections. Recent research has addressed potential newborn screening for SCID. - Altered intracellular and extracellular signaling leads to impaired T-cell functions in ADA-SCID patientsBarbara Cassani
San Raffaele Telethon Institute for Gene Therapy, Milan, Italy
Blood 111:4209-19. 2008Mutations in the adenosine deaminase (ADA) gene are responsible for a form of severe combined immunodeficiency (SCID) caused by the lymphotoxic accumulation of ADA substrates, adenosine and 2'-deoxy-adenosine... - Long-term outcome after hematopoietic stem cell transplantation of a single-center cohort of 90 patients with severe combined immunodeficiencyBenedicte Neven
Unité d Immuno Hématologie et Rhumatologie Pédiatrique, Hopital Necker Enfants Malades, Assistance Publique Hopitaux de Paris, Paris, France
Blood 113:4114-24. 2009Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for severe combined immunodeficiency (SCID)... - A kinase-negative mutation of DNA-PK(CS) in equine SCID results in defective coding and signal joint formationE K Shin
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235, USA
J Immunol 158:3565-9. 1997.... - Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID)P Macchi
Istituto di Tecnologie Biomediche Avanzate, Consiglio Nazionale delle Ricerche, Milano, Italy
Nature 377:65-8. 1995..Both mutations resulted in markedly reduced levels of Jak-3. These findings show that abnormalities in the Jak/STAT signalling pathway can account for SCID in humans... - RAG mutations in human B cell-negative SCIDK Schwarz
Section of Molecular Biology, University of Ulm, D 89070 Ulm, Germany
Science 274:97-9. 1996Patients with human severe combined immunodeficiency (SCID) can be divided into those with B lymphocytes (B+ SCID) and those without (B- SCID)... - Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitutionRebecca H Buckley
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA
Annu Rev Immunol 22:625-55. 2004Mutations in nine different genes have been found to cause the human severe combined immunodeficiency syndrome... - Mutations in the tyrosine phosphatase CD45 gene in a child with severe combined immunodeficiency diseaseC Kung
Howard Hughes Medical Institute, St Louis, Missouri 63110, USA
Nat Med 6:343-5. 2000..The patient presented at 2 months of age with severe combined immunodeficiency disease... - Defective expression of the interleukin-2/interleukin-15 receptor beta subunit leads to a natural killer cell-deficient form of severe combined immunodeficiencyK C Gilmour
Molecular Immunology Unit, Institute of Child Health, University College London, 30 Guilford St, London WC1N 1EH, UK
Blood 98:877-9. 2001..on cytokine signaling, and defects in cytokine receptor complex subunits have been shown to result in severe combined immunodeficiency (SCID) syndromes in humans and in murine models... - Targeted disruption of the catalytic subunit of the DNA-PK gene in mice confers severe combined immunodeficiency and radiosensitivityG E Taccioli
Department of Microbiology, Boston University School of Medicine, Massachusetts 02118, USA
Immunity 9:355-66. 1998..This suggests that the Scid mice may not represent a null phenotype and may retain some residual DNA-PKcs function... - T cell repertoire development in humans with SCID after nonablative allogeneic marrow transplantationMarcella Sarzotti
Department of Immunology, Medicine, and Pediatrics, Duke University Medical Center, Durham, NC 27710, USA
J Immunol 170:2711-8. 2003..The TCR diversity positively correlates in these patients with TREC levels... - Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor gamma chainJ P DiSanto
Institut National de la Sante et de la Recherche Medicale, Unité 132, Hopital Necker Enfants Malades, Paris, France
Proc Natl Acad Sci U S A 92:377-81. 1995..Thus, IL-2R gamma facilitates mainstream B- and T-cell generation and function and also appears to be essential for NK-cell development... - Development of population-based newborn screening for severe combined immunodeficiencyKee Chan
National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA
J Allergy Clin Immunol 115:391-8. 2005BACKGROUND: Severe combined immunodeficiency (SCID) is a treatable, inherited lack of cellular and humoral immunity caused by diverse mutations in several different genes and leading to death in infancy unless immune reconstitution is .. - Population-based newborn screening for severe combined immunodeficiency: steps toward implementationJennifer M Puck
Department of Pediatrics, University of California, San Francisco, CA 94143 0519, USA
J Allergy Clin Immunol 120:760-8. 2007.... - Progress and prospects: gene therapy for inherited immunodeficienciesW Qasim
Molecular Immunology Unit, UCL Institute of Child Health, London, UK
Gene Ther 16:1285-91. 2009..For patients with specific disorders (severe combined immunodeficiency (SCID)-X1, adenosine deaminase deficiency (ADA)-SCID, X-chronic granulomatous disease (CGD) and .. - The different extent of B and T cell immune reconstitution after hematopoietic stem cell transplantation and enzyme replacement therapies in SCID patients with adenosine deaminase deficiencyFederico Serana
Department of Biomedical Science and Biotechnology, University of Brescia, Italy
J Immunol 185:7713-22. 2010.... - Vaccine-acquired rotavirus in infants with severe combined immunodeficiencyNiraj C Patel
Department of Pediatrics, Section of Allergy and Immunology, Baylor College of Medicine, Texas Children s Hospital, Houston, TX 77030, USA
N Engl J Med 362:314-9. 2010..1 month after their first or second rotavirus immunization and subsequently received a diagnosis of severe combined immunodeficiency. Rotavirus was detected, by means of reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay, .. - Intrinsic defects of B cell function in X-linked severe combined immunodeficiencyH White
Molecular Immunology Unit, Institute of Child Health, University College London, GB
Eur J Immunol 30:732-7. 2000..These studies imply that effective humoral reconstitution can only be achieved by the engraftment of normal donor B cells... - Advances in the understanding and treatment of human severe combined immunodeficiencyR H Buckley
Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA
Immunol Res 22:237-51. 2000Human severe combined immunodeficiency (SCID) can result from mutations in any one of at least seven different genes, including those for adenosine deaminase, the common cytokine receptor gamma chain, Janus kinase 3, IL-7 receptor alpha .. - SCID in Jack Russell terriers: a new animal model of DNA-PKcs deficiencyK Meek
College of Veterinary Medicine and Department of Veterinary Pathology, Michigan State University, East Lansing, MI 48824, USA
J Immunol 167:2142-50. 2001.... - Disseminated bacille Calmette-Guérin in Iranian children with severe combined immunodeficiencyMahnaz Sadeghi-Shabestari
Division of Pediatric Immunology and Allergy, Children s Hospital, Tabriz University Medical Sciences, Tabriz, Iran
Int J Infect Dis 13:e420-3. 2009..This study was performed to determine the underlying defects in patients with BCG-osis... - Improving cellular therapy for primary immune deficiency diseases: recognition, diagnosis, and managementLinda M Griffith
Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
J Allergy Clin Immunol 124:1152-60.e12. 2009..with PIDs, we present expert guidance for (1) PID diagnoses that are indications for HCT, including severe combined immunodeficiency disease (SCID), combined immunodeficiency disease, and other non-SCID diseases; (2) the critical .. - Multilineage hematopoietic reconstitution without clonal selection in ADA-SCID patients treated with stem cell gene therapyAlessandro Aiuti
San Raffaele Telethon Institute for Gene Therapy HSR TIGET, Milan, Italy
J Clin Invest 117:2233-40. 2007..These data have important implications for the biology of retroviral vectors, the dynamics of genetically modified HSCs, and the safety of gene therapy... - Matched unrelated bone marrow transplant for T+ combined immunodeficiencyC M Roifman
Division of Immunology and Allergy, The Hospital for Sick Children, Ontario, Canada ickkids ca
Bone Marrow Transplant 41:947-52. 2008..We have shown here that matched unrelated donor BMT is highly effective in curing patients with T+ CID. This mode of treatment should be preferred for patients with T+ CID when a related identical donor is not available... - Adenosine-deaminase-deficient mice die perinatally and exhibit liver-cell degeneration, atelectasis and small intestinal cell deathA A Migchielsen
Laboratory for Molecular Carcinogenesis, Sylvius Laboratories, Leiden University, The Netherlands
Nat Genet 10:279-87. 1995..In humans, absence of ADA causes severe combined immunodeficiency. In contrast, ADA-deficient mice die perinatally with marked liver-cell degeneration, but lack .. - New insights into the pathogenesis of adenosine deaminase-severe combined immunodeficiency and progress in gene therapyAisha V Sauer
San Raffaele Telethon Institute for Gene Therapy HSR TIGET, Italy
Curr Opin Allergy Clin Immunol 9:496-502. 2009Adenosine deaminase (ADA)- deficient severe combined immunodeficiency (SCID) is a complex metabolic and immunological disorder, characterized by a severe immunodeficiency due to the accumulation of purine metabolites in plasma and cells... - Guidelines for implementation of population-based newborn screening for severe combined immunodeficiencyAnne Marie Comeau
New England Newborn Screening Program, UMass Medical School, Jamaica Plain, MA 02130, USA
J Inherit Metab Dis 33:S273-81. 2010b>Severe combined immunodeficiency (SCID) is a Primary Immune Deficiency that is under consideration for population-based newborn screening (NBS) by many NBS programs, and has recently been recommended for inclusion in the US uniform panel .. - Long-term clinical outcome of patients with severe combined immunodeficiency who received related donor bone marrow transplants without pretransplant chemotherapy or post-transplant GVHD prophylaxisMary Dell Railey
Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA
J Pediatr 155:834-840.e1. 2009To determine long-term health benefits of nonablative bone marrow transplantation for severe combined immunodeficiency (SCID), we investigated our cohort of 161 related donor bone marrow-transplanted patients with SCID... - Successful unrelated cord blood transplantation in two children with severe combined immunodeficiency syndromeF Fagioli
Department of Paediatrics, University of Turin, Italy
Bone Marrow Transplant 31:133-6. 2003..No chronic GVHD was observed in either. The patients are alive and well at 53 and 15 months after transplantation. In conclusion, umbilical cord blood represents a valid alternative source of haemopoietic stem cells... - Hematopoietic stem cell transplantation for severe combined immunodeficiency in the neonatal period leads to superior thymic output and improved survivalLaurie A Myers
Duke University Medical Center, Durham, NC 27710, USA
Blood 99:872-8. 2002All genetic types of severe combined immunodeficiency (SCID) can be cured by stem cell transplantation from related donors... - Reticular dysgenesis: HLA non-identical bone marrow transplants in a series of 10 patientsY Bertrand
, , Lyon, France
Bone Marrow Transplant 29:759-62. 2002..These results demonstrate the mandatory need for intensive conditioning before haploidentical HSCT in RD to achieve full lymphoid and myeloid engraftment... - Implementing routine testing for severe combined immunodeficiency within Wisconsin's newborn screening programMei Wang Baker
Wisconsin State Laboratory of Hygiene, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA
Public Health Rep 125:88-95. 2010b>Severe combined immunodeficiency (SCID) is the result of genetic defects that impair normal T-cell development. SCID babies typically appear normal at birth, but acquire multiple life-threatening infections within a few months... - Mutations in genes required for T-cell development: IL7R, CD45, IL2RG, JAK3, RAG1, RAG2, ARTEMIS, and ADA and severe combined immunodeficiency: HuGE reviewLisa Kalman
Centers for Disease Control and Prevention, Newborn Screening Quality Assurance Program, Office of Genomics and Disease Prevention, Atlanta, Georgia, USA
Genet Med 6:16-26. 2004b>Severe combined immunodeficiency (SCID) is an inherited immune disorder characterized by T-cell lymphopenia (TCLP), a profound lack of cellular (T-cell) and humoral (B-cell) immunity and, in some cases, decreased NK-cell number and .. - Atypical X-linked severe combined immunodeficiency due to possible spontaneous reversion of the genetic defect in T cellsV Stephan
, , , Germany
N Engl J Med 335:1563-7. 1996 - Long-term immune reconstitution and outcome after HLA-nonidentical T-cell-depleted bone marrow transplantation for severe combined immunodeficiency: a European retrospective study of 116 patientsE Haddad
Unité d Immunologie et d Hématologie Pédiatriques, Departement de Pediatrie, Hopital Necker Enfants Malades, Paris, France
Blood 91:3646-53. 1998..HLA-nonidentical T-cell-depleted bone marrow transplantation (BMT) performed in 193 patients with severe combined immunodeficiency (SCID) at 18 European centers between December 1982 and December 31, 1993... - Long-term immune reconstitution after anti-CD52-treated or anti-CD34-treated hematopoietic stem cell transplantation for severe T-lymphocyte immunodeficiencyMary A Slatter
Department of Paediatric Immunology, Newcastle upon Tyne Hospitals Foundation Trust, Newcastle upon Tyne, United Kingdom
J Allergy Clin Immunol 121:361-7. 2008..T cell-depleted haploidentical transplantations are successful if there is no HLA-identical donor. Methods to remove T lymphocytes include addition of anti-CD52 antibodies and CD34(+) HSC selection... - Clinical heterogeneity can hamper the diagnosis of patients with ZAP70 deficiencyTuba Turul
Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Dr Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands
Eur J Pediatr 168:87-93. 2009.... - Single-center analysis of long-term outcome after hematopoietic cell transplantation in children with congenital severe T cell immunodeficiencyEvelina Mazzolari
Divisione di Emato Oncologia Pediatrica, Ospedale dei Bambini, Spedali Civili, Brescia, Italy
Immunol Res 44:4-17. 2009..Persistence of a low number of circulating naive T cells and long-term requirement for intravenous immunoglobulin were associated with a higher incidence of clinical events... - X-linked severe combined immunodeficiency: from molecular cause to gene therapy within seven yearsW J Leonard
Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1674, USA
Mol Med Today 6:403-7. 2000X-linked severe combined immunodeficiency (XSCID) is the most common form of SCID... - Canine X-linked severe combined immunodeficiencyP J Felsburg
Department of Clinical Studies Philadelphia, School of Veterinary Medicine, University of Pennsylvania, USA
Vet Immunol Immunopathol 69:127-35. 1999Canine X-linked severe combined immunodeficiency (XSCID) is due to mutations in the common gamma (gamma c) subunit of the IL-2, IL-4, IL-7, IL-9 and IL-15 receptors... - Mutations causing severe combined immunodeficiency: detection with a custom resequencing microarrayTonya Lebet
Department of Pediatrics, University of California San Francisco School of Medicine, San Francisco, California 94143 0519, USA
Genet Med 10:575-85. 2008Mutation diagnosis of severe combined immunodeficiency is challenging because of the multiplicity of disease genes and large number of disease-causing mutations, including unique ones that continue to be found... - A deletion in the gene encoding the CD45 antigen in a patient with SCIDE Z Tchilian
The Edward Jenner Institute for Vaccine Research, Compton, United Kingdom
J Immunol 166:1308-13. 2001.... - Rapid protein-based assays for the diagnosis of T-B+ severe combined immunodeficiencyK C Gilmour
Department of Immunology, Camelia Botnar Laboratories, Great Ormond Street Hospital NHS Trust, Great Ormond Street, London WC1N 3JH, UK
Br J Haematol 112:671-6. 2001..Thus, these protein-based assays have led to rapid molecular diagnoses in T-B+ SCID that have subsequently been confirmed by genetic analysis... - More than just SCID--the phenotypic range of combined immunodeficiencies associated with mutations in the recombinase activating genes (RAG) 1 and 2Tim Niehues
HELIOS Klinikum Krefeld, Center for Child and Adolescent Health, Krefeld, Germany
Clin Immunol 135:183-92. 2010..Thorough assessment and interpretation of clinical and immunological findings will guide treatment modalities as intense as hematopoietic stem cell transplantation... - B-cell function in severe combined immunodeficiency after stem cell or gene therapy: a reviewRebecca H Buckley
Departments of Pediatrics and Immunology, Duke University Medical Center, Durham, NC, USA
J Allergy Clin Immunol 125:790-7. 2010Although bone marrow transplantation has resulted in life-saving T-cell reconstitution in infants with severe combined immunodeficiency (SCID), correction of B-cell function has been more problematic... - Adenosine deaminase deficiency can present with features of Omenn syndromeChaim M Roifman
J Allergy Clin Immunol 121:1056-8. 2008 - Ancestral founder mutation of the nude (FOXN1) gene in congenital severe combined immunodeficiency associated with alopecia in southern Italy populationM Adriani
Department of Pediatrics, Federico II University, Naples, Italy
Ann Hum Genet 68:265-8. 2004..The three haplotypes identified, 3/R255X/3, 3/R255X/2 and 3/R255X/1, are consistent with a single ancestral origin for the mutation R255X... - V(D)J recombination defects in lymphocytes due to RAG mutations: severe immunodeficiency with a spectrum of clinical presentationsA Villa
Department of Human Genome and Multifactorial Disease, Istituto di Tecnologie, Biomediche Avanzate, Consiglio Nazionale delle Ricerche, Segrate, Italy
Blood 97:81-8. 2001b>Severe combined immunodeficiency (SCID) comprises a heterogeneous group of primary immunodeficiencies, a proportion of which are due to mutations in either of the 2 recombination activating genes (RAG)-1 and -2, which mediate the process .. - Jak3 and the pathogenesis of severe combined immunodeficiencyMatthew Husa
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, MSC 1820, 10 Center Drive, Bethesda, MD 20892, USA
Mol Immunol 41:727-37. 2004The discovery that Jak3 mutations are a significant cause of severe combined immunodeficiency (SCID), a rare inherited defect characterized by lymphopenia, has provided valuable insights into the functions of Jak3 in lymphoid development .. - Intrathymic administration of hematopoietic progenitor cells enhances T cell reconstitution in ZAP-70 severe combined immunodeficiencyOumeya Adjali
, Centre National de la Recherche Scientifique, , 34293 Montpellier, France
Proc Natl Acad Sci U S A 102:13586-91. 2005Patients with severe combined immunodeficiency (SCID) present with opportunistic infections that are almost universally fatal in infancy... - Severe combined immunodeficiency caused by deficiency in either the delta or the epsilon subunit of CD3Genevieve De Saint Basile
Unité Développement Normal et Pathologique du Système Immunitaire, INSERM U 429, Paris, France
J Clin Invest 114:1512-7. 2004We investigated the molecular mechanism underlying a severe combined immunodeficiency characterized by the selective and complete absence of T cells. The condition was found in 5 patients and 2 fetuses from 3 consanguineous families... - Gene therapy for severe combined immunodeficiency: are we there yet?Marina Cavazzana-Calvo
INSERM U768 and Université Paris Descartes, Paris, France
J Clin Invest 117:1456-65. 2007..In this review, we summarize the advantages and limitations associated with the use of gene therapy to cure SCID. Insertional mutagenesis and technological improvements aimed at increasing the safety of this strategy are also discussed... - DNA-dependent kinase (p350) as a candidate gene for the murine SCID defectC U Kirchgessner
Department of Radiation Oncology, Stanford University School of Medicine, CA 94305
Science 267:1178-83. 1995..Chromosomal fragments expressing p350 complement the SCID phenotype, and p350 protein levels are greatly reduced in cells derived from SCID mice compared to cells from wild-type mice... - Structural and functional basis for JAK3-deficient severe combined immunodeficiencyF Candotti
Clinical Gene Therapy Branch, National Center for Human Genome Research, National Institutes of Health, Bethesda, MD, USA
Blood 90:3996-4003. 1997Mutations of the Janus family kinase JAK3 have been found to be responsible for autosomal recessive severe combined immunodeficiency (SCID) in humans... - Highly restricted human T cell repertoire in peripheral blood and tissue-infiltrating lymphocytes in Omenn's syndromeF Rieux-Laucat
Unité INSERM 429, Hopital Necker Enfants Malades, 75743 Paris, Cedex 15, France
J Clin Invest 102:312-21. 1998..These results suggest that the oligoclonal expansion of T cells observed in Omenn's syndrome could be the consequence of autoimmune proliferation generated by a profound defect in lymphocyte development... - T lymphocyte-directed gene therapy for ADA- SCID: initial trial results after 4 yearsR M Blaese
National Center for Human Genome Research, National Institutes of Health NIH, Bethesda, MD 20892, USA
Science 270:475-80. 1995..transfer of the adenosine deaminase (ADA) gene into the T cells of two children with severe combined immunodeficiency (ADA- SCID). The number of blood T cells normalized as did many cellular and humoral immune responses... - In vivo correction of ZAP-70 immunodeficiency by intrathymic gene transferOumeya Adjali
, , Montpellier, France
J Clin Invest 115:2287-95. 2005..Thus, intrathymic injection of a lentiviral vector could represent a simplified and potentially safer alternative to ex vivo gene-modified hematopoietic stem cell transplantation for gene therapy of T cell immunodeficiencies... - Gene therapy for severe combined immunodeficienciesH Bobby Gaspar
Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK
Expert Opin Biol Ther 5:1175-82. 2005..These side effects are now being studied in detail and measures to prevent such events through alternative vectors delivery systems are in development at present... - Comparison of five retrovirus vectors containing the human IL-2 receptor gamma chain gene for their ability to restore T and B lymphocytes in the X-linked severe combined immunodeficiency mouse modelG J Avilés Mendoza
Hematopoiesis Section, National Institutes of Health, Bethesda, Maryland 20892, USA
Mol Ther 3:565-73. 2001X-linked severe combined immunodeficiency (XSCID) is caused by mutations in the IL-2 receptor gamma chain (IL2RG) gene, resulting in absent T lymphocytes and nonfunctional B lymphocytes... - Retroviral transduction of IL-7Ralpha into IL-7Ralpha-/- bone marrow progenitors: correction of lymphoid deficiency and induction of neutrophiliaQ Jiang
Laboratory of Molecular Regulation, National Cancer Instutute, NIH, Frederick, MD 21702-1201, USA
Gene Ther 12:1761-8. 2005Defects in the gene for the IL-7 receptor (R) alpha chain are one cause of severe combined immunodeficiency disease (SCID) based on a strict requirement for IL-7 in T lymphoid development and survival... - Molecular defects in T- and B-cell primary immunodeficiency diseasesCharlotte Cunningham-Rundles
Division of Clinical Immunology, Mount Sinai School of Medicine, 1425 Madison Avenue, Box 1089, New York, New York 10029, USA
Nat Rev Immunol 5:880-92. 2005..The prospect of gene therapy continues to be included in the armamentarium of treatment considerations, because these conditions could be among the first to benefit from gene-therapy trials in humans... - Purified hematopoietic stem cell engraftment of rare niches corrects severe lymphoid deficiencies without host conditioningDeepta Bhattacharya
Department of Pathology, Institute of Cancer and Stem Cell Biology and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
J Exp Med 203:73-85. 2006..These experiments provide a general mechanism by which transplanted HSCs can correct hematopoietic deficiencies without any host conditioning or with only highly specific and transient lymphoablation... - A new direction for gene therapy: intrathymic T cell-specific lentiviral gene transferRuth Seggewiss
National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland 20892, USA
J Clin Invest 115:2064-7. 2005.... - [Severe combined immunodeficiency diseases]Shigeru Tsuchiya
Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University
Nippon Rinsho 63:565-9. 2005 - Silencing p21(Waf1/Cip1/Sdi1) expression increases gene transduction efficiency in primitive human hematopoietic cellsJ Zhang
Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
Gene Ther 12:1444-52. 2005..Decreasing p21 expression transiently while increasing gene-transfer vector integration may ultimately facilitate clinical applications of gene therapy... - Treatment of an infant with X-linked severe combined immunodeficiency (SCID-X1) by gene therapy in AustraliaSamantha L Ginn
Gene Therapy Research Unit, The Children's Hospital at Westmead and Children's Medical Research Unit, Sydney, NSW
Med J Aust 182:458-63. 2005OBJECTIVE: To report the outcome of gene therapy in an infant with X-linked severe combined immunodeficiency (SCID-X1), which typically causes a lack of T and natural killer (NK) cells... - Rapid and efficient homing of human CD34(+)CD38(-/low)CXCR4(+) stem and progenitor cells to the bone marrow and spleen of NOD/SCID and NOD/SCID/B2m(null) miceO Kollet
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel
Blood 97:3283-91. 2001..This study reveals rapid and efficient homing to the murine bone marrow by primitive human CD34(+)CD38(-/low)CXCR4(+) cells that is integrin mediated and depends on activation of the protein kinase C signal transduction pathway by SDF-1... - [Substitution therapy with hematopoietic progenitors in the primary immunodeficiencies]T Espanol
Unidad de Inmunologia, Hospital Vall d Hebron, Barcelona
Allergol Immunopathol (Madr) 29:118-21. 2001..We also discuss the differences observed according to the vectors used and the underlying disease... - Gene therapy for severe combined immunodeficiencyMarina Cavazzana-Calvo
Département de Biothérapie, Hopital Necker Enfants Malades, 75015 Paris, France
Annu Rev Med 56:585-602. 2005Studies of severe combined immunodeficiency (SCID), a group of rare monogenic disorders, have provided key findings about the physiology of immune system development... - Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped gammaretroviral vectorH Bobby Gaspar
Molecular Immunology Unit, Institute of Child Health, University College London, London, UK
Lancet 364:2181-7. 2004BACKGROUND: X-linked severe combined immunodeficiency (SCID-X1) is caused by mutations in the common cytokine-receptor gamma chain (gamma(c)), resulting in disruption of development of T lymphocytes and natural-killer cells... - Serial transplantations in nonobese diabetic/severe combined immunodeficiency mice of transduced human CD34+ cord blood cells: efficient oncoretroviral gene transfer and ex vivo expansion under serum-free conditionsLoretta Gammaitoni
Institute for Cancer Research and Treatment, Laboratory of Clinical Oncology, 10060 Candiolo, Torino, Italy
Stem Cells 24:1201-12. 2006..These cells engrafted up to three generations of serially transplanted nonobese diabetic/severe combined immunodeficiency mice: 54.26% +/- 5.59%, 19.05% +/- 2.01%, and 6.15% +/- 5... - [Gene therapy for primary immunodeficiency diseases]Tadashi Ariga
Department of Pediatrics, Hokkaido University Graduate School of Medicine
Nippon Rinsho 63:641-5. 2005 - [Gene therapy of severe combined immunodeficiency disease: proof of principle of efficiency and safety issues. Gene therapy, primary immunodeficiencies, retrovirus, lentivirus, genome]Alain Fischer
INSERM U 429, Unité d Immunologie et Hématologie Pédiatrique et Département de Biothérapie, Hopital Necker Enfants Malades, 149 rue de Sevres, 75015 Paris
Bull Acad Natl Med 189:779-85; discussion 786-8. 2005..Vector modifications, based mostly on inactivating the enhancer activity of the LTR, should preserve efficacy while improving safety...
Research Grants
- Varicella-Zoster Virus: T Cell/Skin Tropism & ImmunityAnn M Arvin; Fiscal Year: 2010..by investigating VZV infection of human skin, T cell and dorsal root ganglia xenografts in the severe combined immunodeficiency (SCID) mouse model...
- MECHANISMS OF ALLOGENEIC STEM CELL EDUCATION IN SCIDRebecca H Buckley; Fiscal Year: 2010..immune reconstitution (16 HLA-identical, investigate identical in patients with severe combined immunodeficiency (SCID) given transplants of rigorously T cell-depleted HLA- The overall goal of the proposed research ..
- Molecular Recognition Studies of the Interleukin-7 PathwaySCOTT T WALSH; Fiscal Year: 2010..Under- and over-stimulation of the IL-7 pathway has been implicated in the pathogenesis of a form of severe combined immunodeficiency, autoimmune conditions, coronary artery disease, and several cancers...
- Molecular Recognition Studies of the Interleukin-7 PathwayScott Walsh; Fiscal Year: 2009..Under- and over-stimulation of the IL-7 pathway has been implicated in the pathogenesis of a form of severe combined immunodeficiency, autoimmune conditions, coronary artery disease, and several cancers...
- METVAN: A Novel Anticancer AgentOSMOND D CRUZ; Fiscal Year: 2003..exhibits significant antitumor activity, delays tumor progression and prolongs survival time in severe combined immunodeficiency (SCID) mouse xenograft models of human malignant glioblastoma and breast cancer...
- Gene Therapy for Purine Nucleoside Phosphorylase Deficiency (PNP)Kevin Baker; Fiscal Year: 2007..The first was a French trial of retroviral gene therapy for X-linked severe combined immunodeficiency (SCID), in which bone marrow cells from children deficient in the common gamma-chain for several ..
- Adenosine Deaminase, Adenosine Signaling and DiseaseRODNEY KELLEMS; Fiscal Year: 2006..However, despite many years of investigation the molecular basis of the severe combined immunodeficiency resulting from ADA deficiency is not understood...
- INTERLEUKIN 2 RECEPTOR AND T LYMPHOCYTE GROWTHTHOMAS MALEK; Fiscal Year: 1999..development as mutations in the human gamma-c gene has been causally associated with X- linked severe combined immunodeficiency disease (SCID)...
- Vector Insertion and Mutagenesis in Human HematopoiesisChristof von Kalle; Fiscal Year: 2007..has been used to correct genetic defects most successfully in patients with potentially fatal human severe combined immunodeficiency disease (SCID)...
- ADENOSINE DEAMINASE DEFICIENCYLinda Thompson; Fiscal Year: 2007Mutations in the gene for adenosine deaminase (ADA) cause severe combined immunodeficiency in humans. ADA-deficient patients exhibit a profound lymphopenia and are susceptible to a wide array of infectious agents...
- Strategies Against HPV Related Genital Diseases in WomenBradley Monk; Fiscal Year: 2006..D., Dr. Monk will evaluate co-carcinogens and anti-viral agents in a recently described severe combined immunodeficiency mouse model using implanted human HPV infected epithelium, cervical intraepithelial neoplasia (CIN)...